Study of 177Lu Human Monoclonal Antibody 5B1 (MVT-1075) in Combination With a Blocking Dose of MVT-5873 as Radioimmunotherapy

NCT ID: NCT03118349

Last Updated: 2023-04-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-01
• Study Completion Date: 2018-04-11

Brief Summary

Open label, nonrandomized, dose-escalation with cohort expansion study of MVT-5873/MVT-1075 in subjects with previously treated, Carbohydrate Antigen 19-9 (CA19-9) positive malignancies (e.g., pancreatic adenocarcinoma).

Detailed Description

Open label, nonrandomized, dose escalation study of MVT-5873/MVT-1075 to evaluate safety, dosimetry, determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D), and define the pharmacokinetics of MVT-1075. The population consisted of subjects with CA19-9 positive malignancies (i.e., predominately pancreatic adenocarcinoma) who may benefit from a CA19-9-based radioimmunotherapy.

The study utilized a 3+3 study design to identify the MTD. The RP2D was planned to be no higher than the MTD. An expansion group was planned to receive MVT-5873/MVT-1075 at the RP2D in order to obtain initial estimates of response and additional information on safety.

Conditions

Pancreatic Carcinoma; Tumors That Express CA 19-9

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Escalation Cohorts

MVT-5873 blocking dose and MVT-1075 dose escalation; Initial to maximum tolerated dose

Group Type: EXPERIMENTAL

MVT-1075

Intervention Type: DRUG

MVT-1075 administered in two fractions, with each administration of MVT-1075 preceded by blocking dose of MVT-5873.

MVT-5873

Intervention Type: DRUG

MVT-5873 administered intravenously as a non-radioactive blocking agent prior to administration of MVT-1075.

Expansion Cohort - no subjects enrolled

MVT-5873 blocking dose and MVT-1075 Maximum tolerated dose

Group Type: EXPERIMENTAL

MVT-1075

Intervention Type: DRUG

MVT-1075 administered in two fractions, with each administration of MVT-1075 preceded by blocking dose of MVT-5873.

MVT-5873

Intervention Type: DRUG

MVT-5873 administered intravenously as a non-radioactive blocking agent prior to administration of MVT-1075.

Interventions

MVT-1075

MVT-1075 administered in two fractions, with each administration of MVT-1075 preceded by blocking dose of MVT-5873.

Intervention Type: DRUG

MVT-5873

MVT-5873 administered intravenously as a non-radioactive blocking agent prior to administration of MVT-1075.

Intervention Type: DRUG

Other Intervention Names

177Lu-CHX-A"-DTPA-HuMab-5B1; HuMab-5B1

Eligibility Criteria

Inclusion Criteria

1. Signed, informed consent

2. Age 18 or more years

3. Histologically or cytologically confirmed, previously treated, locally-advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) or other CA19-9 positive malignancies

4. Prior treatment with (or intolerance to) at least one standard systemic regimen for the patient's respective tumor

5. Evidence of tumor expression of CA19-9 based on immunohistochemistry performed on tumor samples or elevated serum levels (≥1.5 x upper limits of normal [ULN]) of CA19-9 considered secondary to tumor

6. Evaluable or measurable disease based on RECIST 1.1

7. Recovered from any prior treatment related toxicity to at least Grade 1 with exception of Grade 2 alopecia or other Grade 2 toxicity with prior approval of the Medical Monitor

8. If previously exposed to irradiation, the combined prior and anticipated exposure for Cycle 1 is not expected to exceed organ exposure limits outlined in the study protocol

9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, or Karnofsky performance status (KPS) of 100% to 80%

10. Adequate hematologic, renal and hepatic laboratory parameters

11. Willingness to participate in collection of pharmacokinetic samples

12. Willingness to use adequate contraception throughout study and for a period of 3 months after last dose of MVT-5873 or MVT-1075 (whichever is later)

Exclusion Criteria

1. Brain metastases unless previously treated and well controlled for at least 3 months

2. Any tumor mass greater than 10 cm in longest diameter

3. Other known active cancer(s) likely to require treatment in the next two years

4. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy

5. Prior radiation therapy encompassing more than 25% of the skeleton or prior treatment with 89Strontium or 153Samarium

6. Fewer than 28 days from prior anticancer therapy including chemotherapy, hormonal, investigational, and/or biological therapies and irradiation except for:

1. Ongoing hormonal therapy administered for control of cancer (e.g., breast cancer, prostate cancer), which may be continued throughout the study

2. MVT-5873 and MVT-2163 administered as part of a different protocol

7. Major surgery other than diagnostic surgery within 28 days of Study Day 1

8. History of anaphylactic reaction to human, or humanized, antibody

9. Pregnant or currently breast-feeding

10. Known to be positive for human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C

11. Psychiatric illness/social situations that would interfere with compliance with study requirements

12. Significant cardiovascular risk including, but not limited to, recent (within 4 weeks) coronary stenting or myocardial infarction within 6 months

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BioNTech Research & Development, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

BioNTech Responsible Person

Role: STUDY_DIRECTOR

BioNTech SE

Locations

HonorHealth Research Institute

Scottsdale, Arizona, United States

MSKCC

New York, New York, United States

Countries

United States

References

Tully KM, Tendler S, Carter LM, Sharma SK, Samuels ZV, Mandleywala K, Korsen JA, Delos Reyes AM, Piersigilli A, Travis WD, Sen T, Pillarsetty N, Poirier JT, Rudin CM, Lewis JS. Radioimmunotherapy Targeting Delta-like Ligand 3 in Small Cell Lung Cancer Exhibits Antitumor Efficacy with Low Toxicity. Clin Cancer Res. 2022 Apr 1;28(7):1391-1401. doi: 10.1158/1078-0432.CCR-21-1533.

Reference Type: DERIVED

PMID: 35046060 (View on PubMed)

Other Identifiers

MV-0916-CP-001.01

Identifier Type: -

Identifier Source: org_study_id